These studies are targeted towards understanding the pathogenesis of psoriatic arthritis and the development of specific immunotherapies for psoriatic arthritis, a relatively common chronic inflammatory disease affecting skin and joints. Patients with known or suspected psoriatic arthritis are evaluated at the Clinical Center. Studies include characterization of the clinical and laboratory features of the disease, research studies of the natural history and pathogenesis, genetic studies, and determination of the patients eligibility to enter experimental therapeutic protocols. Patients are asked to contribute blood, skin or synovial membrane samples for immunologic and genetic research studies. Immunologic studies include investigations of 1) the relative importance of monocyte and T cell-derived cytokines in the disease process, 2) the role of cognate interaction between T cells and epidermal or synovial cells, 3) the T cell antigen receptor repertoire in the peripheral blood and at sites of inflammation (i.e., skin and joints, and 4) the recruitment and homing of leukocytes to joints and skin. Our studies so far suggest that in psoriatic arthritis, a small number of antigenic epitopes are driving the T cell responses at sites of inflammation. In contrast to rheumatoid arthritis, T cell-derived cytokines such as IL-2 and IFN-g are commonly found. Activated T cells contribute to the observed pathology not only by releasing cytokines which activate resident cells of these tissues, but also via cognate interactions, which are mediated through cell surface molecules. These findings confirm the important role of T cells in the pathogenesis of psoriatic arthritis and suggest that T cell-directed therapies may be beneficial in treating this disease. Moreover, these findings point out important differences between psoriatic and rheumatoid arthritis and suggest that psoriatic arthritis is a disease entity distinct from other types of inflammatory arthritides.